Transcription-coupled repair
- Transcription-coupled repair
Transcription-coupled repair is a DNA repair mechanism which operates in tandem with transcription. The activity of TCR has been known for 20 years, but its mechanism of action is an area of current research. Failure of the transcription-coupled repair is the cause of Cockayne syndrome, an extreme form of accelerated aging that is fatal early in life.
Mechanism
Genes are copied from DNA to make messenger RNA to instruct protein synthesis by RNA polymerase II. When RNA polymerase finds a lesion in the DNA, like those caused by UV light it stops and the gene is not transcribed. TCR is associated with RNA polymerase II, and the stalled RNAP is the trigger for TCR both in prokaryotes and eukaryotes.
Researchers looked at the CSB protein, which is mutated in patients with Cockayne syndrome, and found that it associated with XPG (another protein associated with the syndrome) and found that RNA polymerase II is stalled during transcription, XPG and CSB respond to the stalled transcription bubble. They then recruit transcription factor II H and other proteins and protein complexes to remodel RNA polymerase, gain access to the bubble, and repair the lesion while leaving polymerase in place.
Other repair mechanisms are possible but less accurate and efficient.
TCR also exists in bacteria, and is mediated by the TRCF (Mfd) protein. TRCF is an SF2 ATPase that uses ATP hydrolysis to translocate on dsDNA upstream of the transcription bubble and forward translocate RNA Polymerase, thus initiating dissociation of the RNA Polymerase ternary elongation complex. TRCF also recruits the Uvr(A)BC nucleotide excision repair machinery by direct physical interaction with the UvrA subunit.
References
*Sarker, A. H. et al. 2005. Recognition of RNA Polymerase II and Transcription Bubbles by XPG, CSB, and TFIIH: Insights for Transcription-Coupled Repair and Cockayne Syndrome "Molecular Cell" 20:187-198
*Deaconescu, A.M. et al. 2006. Structural basis for bacterial transcription-coupled DNA repair. Cell 124(3):507-520
*Deaconescu, A.M., Savery, N.J., Darst, S.A. The bacterial transcription-repair coupling factor. Curr Opin Struct Biol (2007) 1:96-102
Wikimedia Foundation.
2010.
Look at other dictionaries:
transcription-coupled repair — (TCR) the form of nucleotide excision repair (q.v.) acting on the transcribed strand of genes; blocking of RNA polymerase progression by DNA damage initiates the repair process. Mutations affecting this pathway have been associated with Cockayne… … Medical dictionary
Nucleotide excision repair — Diagram[1] Nucleotide excision repair is a DNA repair mechanism.[2] DNA constantly requires r … Wikipedia
DNA repair — For the journal, see DNA Repair (journal). DNA damage resulting in multiple broken chromosomes DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human… … Wikipedia
DNA mismatch repair — is a system for recognizing and repairing erroneous insertion, deletion and mis incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage.[1][2] Mismatch repair is strand… … Wikipedia
Postreplication repair — is the repair of damage to the DNA that takes place after replication. Some example genes in humans include: BRCA2 and BRCA1 BLM NBS1 DNA damage prevents the normal enzymatic synthesis of DNA by the replication fork.[1][2][3][4] … Wikipedia
Excision repair — is a term applied to several DNA repair mechanisms.Excision repair mechanisms that remove the damaged nucleotide replacing it with an undamaged nucleotide complementary to the nucleotide in the undamaged DNA strand. These include: *Base excision… … Wikipedia
nucleotide excision repair — (NER) repair of bulky lesions introduced into DNA by damage, such as that induced by ultraviolet light; at least 30 proteins are involved and the process consists of recognition of the lesion, strand separation at the site, single strand incision … Medical dictionary
global genome repair — (GGR) the form of nucleotide excision repair (q.v.) occurring throughout the genome; a complex of proteins identifies DNA damage by detection of distortions in the DNA helix. A variety of mutations affecting this pathway have been associated with … Medical dictionary
AP-1 (transcription factor) — In molecular biology, the activator protein 1 (AP 1) is a transcription factor which is a heterodimeric protein composed of proteins belonging to the c Fos, c Jun, ATF and JDP families. AP 1 upregulates transcription of genes containing the TPA… … Wikipedia
ERCC8 (gene) — Excision repair cross complementing rodent repair deficiency, complementation group 8, also known as ERCC8, is a human gene.cite web | title = Entrez Gene: ERCC8 excision repair cross complementing rodent repair deficiency, complementation group… … Wikipedia
